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The Cochrane Database of Systematic... Aug 2021Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on... (Review)
Review
BACKGROUND
Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. So far, systemic corticosteroids are one of the few treatment options for COVID-19. Nonetheless, size of effect, certainty of the evidence, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.
OBJECTIVES
To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID-19, and to keep up to date with the evolving evidence base using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19, irrespective of disease severity, participant age, gender or ethnicity. We included any type or dose of systemic corticosteroids. We included the following comparisons: systemic corticosteroids plus standard care versus standard care (plus/minus placebo), dose comparisons, timing comparisons (early versus late), different types of corticosteroids and systemic corticosteroids versus other active substances. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome or Middle East respiratory syndrome), corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality, ventilator-free days, new need for invasive mechanical ventilation, quality of life, serious adverse events, adverse events, and hospital-acquired infections.
MAIN RESULTS
We included 11 RCTs in 8075 participants, of whom 7041 (87%) originated from high-income countries. A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 2322). We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry, but without results yet. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 10 RCTs (7989 participants), one of which did not report any of our pre-specified outcomes and thus our analysis included outcome data from nine studies. All-cause mortality (at longest follow-up available): systemic corticosteroids plus standard care probably reduce all-cause mortality slightly in people with COVID-19 compared to standard care alone (median 28 days: risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.80 to 1.00; 9 RCTs, 7930 participants; moderate-certainty evidence). Ventilator-free days: corticosteroids may increase ventilator-free days (MD 2.6 days more than control group rate of 4 days, 95% CI 0.67 to 4.53; 1 RCT, 299 participants; low-certainty evidence). Ventilator-free days have inherent limitations as a composite endpoint and should be interpreted with caution. New need for invasive ventilation: the evidence is of very low certainty. Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics. Quality of life/neurological outcome: no data were available. Serious adverse events: we included data on two RCTs (678 participants) that evaluated systemic corticosteroids compared to standard care (plus/minus placebo); for adverse events and hospital-acquired infections, we included data on five RCTs (660 participants). Because of high risk of bias, heterogeneous definitions, and underreporting we are uncertain about the size and direction of the effects. Consequently, we did not perform analysis beyond the presentation of descriptive statistics (very low-certainty evidence). Different types, dosages or timing of systemic corticosteroids We identified one study that compared methylprednisolone with dexamethasone. The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants (n = 86). No data were available for the other outcomes. We did not identify comparisons of different dosages or timing. Outpatients with asymptomatic or mild disease Currently, there are no studies published in populations with asymptomatic infection or mild disease.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence shows that systemic corticosteroids probably slightly reduce all-cause mortality in people hospitalised because of symptomatic COVID-19. Low-certainty evidence suggests that there may also be a reduction in ventilator-free days. Since we are unable to adjust for the impact of early death on subsequent endpoints, the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions. Currently, there is no evidence for asymptomatic or mild disease (non-hospitalised participants). There is an urgent need for good-quality evidence for specific subgroups of disease severity, for which we propose level of respiratory support at randomisation. This applies to the comparison or subgroups of different types and doses of corticosteroids, too. Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable. We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future. Most ongoing studies target people who need respiratory support at baseline. With the living approach of this review, we will continue to update our search and include eligible trials and published data.
Topics: Adrenal Cortex Hormones; COVID-19; Humans; Immunization, Passive; Randomized Controlled Trials as Topic; Respiration, Artificial; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34396514
DOI: 10.1002/14651858.CD014963 -
Gynecologic Oncology Jun 2022Adoptive cell therapy (ACT) has shown promise in hematologic and solid tumors. While data supports immunogenicity of gynecologic cancers, the benefit of ACT is not yet... (Meta-Analysis)
Meta-Analysis Review
Adoptive cell therapy (ACT) has shown promise in hematologic and solid tumors. While data supports immunogenicity of gynecologic cancers, the benefit of ACT is not yet clear. To address this question, we performed a comprehensive systematic review and meta-analysis. Eligible studies included those reporting oncologic response or toxicity data in at least one patient with any gynecologic cancer treated with ACT. Chi-square test and multivariable logistic regression were performed to identify predictors of response. We retrieved 281 articles, and 28 studies met our inclusion criteria. These comprised of 401 patients including 238 patients with gynecologic cancers (61.8% ovarian, 34.0% cervical, 2.9% endometrial, and 1.2% other). In patients with gynecologic cancers, response rates to ACT were 8.1% complete response, 18.2% partial response, and 31.4% stable disease, for an objective response rate (ORR) of 26.3%, disease control rate (DCR) of 57.6%, and median response duration of 5.5 months. Patients in studies reporting ≤1 median line of prior therapy had a higher ORR (52.9% vs. 22.6% for >1, p < 0.001), although DCR in the >1 group was still 53.2%. ORRs by ACT type were tumor infiltrating lymphocytes (TIL) 41.4%, natural killer cells 26.7%, peripheral autologous T-cells 18.4%, T-cell receptor-modified T-cells 15.4%, and chimeric antigen receptor T-cells 9.5% (p = 0.001). ORR was significantly improved with inclusion of lymphodepletion (34.8% vs. 15.4% without, p = 0.001). On multivariable analysis controlling for cancer type and lymphodepletion, TIL therapy was predictive of objective response (odds ratio 2.6, p = 0.011). The rate of grade 3 or 4 toxicity was 46.0%. All grade adverse events included fever, hypotension, dyspnea, confusion, hematologic changes, nausea/vomiting, fatigue, and diarrhea. In conclusion, ACT is a promising treatment modality in gynecologic cancer. We observed a particular benefit of TIL therapy and suggest inclusion of lymphodepletion in future trials.
Topics: Cell- and Tissue-Based Therapy; Female; Genital Neoplasms, Female; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Receptors, Antigen, T-Cell
PubMed: 35400527
DOI: 10.1016/j.ygyno.2022.03.013 -
BMJ (Clinical Research Ed.) Sep 2021To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).
DESIGN
Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.
DATA SOURCES
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).
STUDY SELECTION
Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.
METHODS
After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.
RESULTS
As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) -4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD -4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD -3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD -4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.
CONCLUSION
In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.
SYSTEMATIC REVIEW REGISTRATION
This review was not registered. The protocol established a priori is included as a data supplement.
FUNDING
This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).
READERS' NOTE
This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (www.covid19lnma.com).
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antiviral Agents; Bayes Theorem; COVID-19; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Humans; Immunization, Passive; Network Meta-Analysis; SARS-CoV-2; Treatment Outcome; COVID-19 Serotherapy
PubMed: 34556486
DOI: 10.1136/bmj.n2231 -
The Oncologist Jun 2023T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
METHODS
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
RESULTS
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
CONCLUSION
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Topics: Male; Humans; Melanoma; Skin Neoplasms; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Melanoma, Cutaneous Malignant
PubMed: 37036865
DOI: 10.1093/oncolo/oyad078 -
Viruses Mar 2023While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent... (Meta-Analysis)
Meta-Analysis Review
While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.
Topics: Humans; COVID-19; COVID-19 Serotherapy; Randomized Controlled Trials as Topic; Immunization, Passive; Pandemics
PubMed: 36992474
DOI: 10.3390/v15030765 -
International Journal of Molecular... Sep 2023The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and... (Review)
Review
The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin's lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy.
Topics: Humans; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Programmed Cell Death 1 Receptor; Neoplasm Recurrence, Local; Hematologic Neoplasms; Immunotherapy, Adoptive; T-Lymphocytes
PubMed: 37834228
DOI: 10.3390/ijms241914780 -
Frontiers in Immunology 2021Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications....
Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future. Systematic Review Registration.
Topics: Animals; Autoimmune Diseases; Communicable Diseases; Humans; Immunomodulation; Molecular Imaging; Molecular Targeted Therapy; Neoplasms; Recombinant Proteins; Single-Domain Antibodies
PubMed: 35116045
DOI: 10.3389/fimmu.2021.838082 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
International Journal of Clinical... Oct 2021Background Vaccination plays an important role in the prevention of influenza. Channels that improve vaccination adherence can play a vital part in improving patient... (Meta-Analysis)
Meta-Analysis Review
Background Vaccination plays an important role in the prevention of influenza. Channels that improve vaccination adherence can play a vital part in improving patient care. This study seeks to inform the design and implementation of pharmacy interventions at scale on improving influenza vaccination rates. Aim of the review The aim of this study was to identify key success factors for effective pharmacy intervention design and implementation to improve vaccination acceptance rates in influenza. Methods A systematic search of MEDLINE, Embase, and Cochrane CENTRAL was performed to find literature on influenza vaccinations delivered at pharmacies, pharmacist-delivered influenza vaccinations, or influenza vaccination campaigns originating in the pharmacy setting. A meta-analysis using a random effects model estimated the impact of pharmacy intervention on vaccination rates (assessed as relative risk [RR] and 95% confidence intervals [95% CI]). Results A total of 1221 studies were found that met the search criteria, of which 12 were selected for the literature review following eligibility screening. A meta-analysis of studies that contained binary total population and vaccination rate data was conducted on 6 studies, including 3182 participants, the vaccination rate was 24% higher in those who used the pharmacy-based intervention compared with those who used standard care [RR (95% CI) 1.24 (1.05, 1.47)]. Two separate sensitivity analyses were run for the vaccination rate. In participants aged ≥ 65 years, the vaccination rate was 3% higher in those who received the pharmacy-based intervention compared with those who received standard care; however, this change was not significant [RR (95% CI) 1.03 (0.86, 1.24)]. Additionally, a qualitative review showed that more successful pharmacy-based interventions were those with the more active involvement of pharmacists in routine care. This included regular checkup of vaccine status, proactive conversations and recommendations about vaccination, and pharmacy-based immunization programs, with specific vaccination days. In-pharmacy communication rather than passive information, such as through leaflets and posters was also more effective. Conclusion Pharmacists can play a significant role to improve patient treatment, adherence, and outcomes associated with influenza vaccines. Once pharmacy-based immunization is established, proactive involvement of is key to ensure successful program implementation and results. Expanding access for pharmacists and pharmacy intervention to provide vaccinations may increase vaccination acceptance and could be a valuable intervention in patient care. Additional studies should consider high-risk populations to inform optimal design and implementation strategies.
Topics: Aged; Community Pharmacy Services; Humans; Influenza Vaccines; Influenza, Human; Pharmacies; Pharmacists; Pharmacy; Vaccination
PubMed: 34047881
DOI: 10.1007/s11096-021-01250-1 -
Influenza and Other Respiratory Viruses Mar 2020A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non-corticosteroid immunomodulatory therapy and potential adverse effects.
METHOD
We searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi-RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type/subtype or age of participants. Where possible, we pooled estimates of effect using random-effects meta-analysis models.
RESULTS
We identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and/or non-steroidal anti-inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta-analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37-1.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05-1.92). There was a significant reduction in mortality associated with macrolides and/or NSAIDs (OR 0.28; 0.10-0.77).
CONCLUSIONS
Passive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high-quality RCTs with sufficient statistical power to address this evidence gap.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Hospitalization; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunization, Passive; Immunologic Factors; Inflammation; Influenza, Human; Mortality; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 31733048
DOI: 10.1111/irv.12699